Antibody-based therapies have proven effective treatments for some diseases but in some cases, toxicities due to broad target expression have limited their therapeutic effectiveness. In addition, antibody-based therapeutics have exhibited other limitations such as rapid clearance from the circulation following administration. Conjugating agents to antibodies has been used to further advance the use of antibody-based therapies. Molecules such as toxins, radionuclides and drugs including anti-cancer drugs have been conjugated to certain antibodies to generate immunotoxins, radioimmunoconjugates, and/or antibody-drug conjugates (ADCs).
In the realm of small molecule therapeutics, strategies have been developed to provide prodrugs of an active chemical entity. Such prodrugs are administered in a relatively inactive (or significantly less active) form. Once administered, the prodrug is metabolized in vivo into the active compound. Such prodrug strategies can provide for increased selectivity of the drug for its intended target and for a reduction of adverse effects.
Accordingly, there is a continued need in the field of antibody-based therapeutics for antibodies that mimic the desirable characteristics of the small molecule prodrug, as well as a need for improved methods of conjugating agents to these antibodies without negatively impacting their ability to mimic the desirable characteristics of the small molecule prodrug.